The mitochondrion in eukaryotes is the organelle responsible for cellular respiration, and is unique among animal organelles in that it possess its own DNA coding genome. In the fruitfly genus Drosophila, as in humans, this genome consists of a circular molecule about 16 Kb in size, which is maternally inherited and non-recombining. It has been noted that several human diseases appear to be related to mutational aberrations in the mitochondrial DNA genome but, our understanding of the normal mutational processes occurring in mtDNA are poorly understood. Consequently, knowledge concerning the usual mutational process in a model system, such as Drosophila, would be of great interest. To understand the mutational variation found in Drosophila, sequence variation at eight protein coding mitochondrial genes within natural populations and among different species will be examined to determine the factors influencing the levels of variation. This will be accomplished by testing the evidence in two separate ways: (1) By examining whether sequence variation observed within populations of Drosophila is due to the accumulation of neutral mutations, or the result of mutational substitutions that are maintained by natural selection. This will be tested by using population genetic models based on neutral theory and coalescent theory. (2) By examining the factors affecting sequence variation in these genes among different species of Drosophila, which will be tested by using comparative phylogenetic tree methods.